“Matreshka” genes with alternative reading frames

2016 ◽  
Vol 52 (2) ◽  
pp. 125-140
Author(s):  
E. V. Sheshukova ◽  
A. V. Shindyapina ◽  
T. V. Komarova ◽  
Yu. L. Dorokhov
Keyword(s):  
Alternative Reading Frames ◽  
Alternative Reading ◽  
Reading Frames

scholarly journals Limited, but potentially functional translation of non-coding transcripts in the HEK293T cellular cytosol

2021 ◽  
Author(s):  
Annelies Bogaert ◽  
Daria Fijalkowska ◽  
An Staes ◽  
Tessa Van de Steene ◽  
Hans Demol ◽  
...  
Keyword(s):  
Search Space ◽  
Ribosome Profiling ◽  
Spectrometric Analysis ◽  
Novel Proteins ◽  
Coding Regions ◽  
Functional Potential ◽  
Non Coding Rnas ◽  
Alternative Reading Frames ◽  
Alternative Reading ◽  
Reading Frames

Ribosome profiling has revealed translation outside of canonical coding sequences (CDSs) including translation of short upstream ORFs, long non-coding RNAs, overlapping ORFs, ORFs in UTRs or ORFs in alternative reading frames. Studies combining mass spectrometry, ribosome profiling and CRISPR-based screens showed that hundreds of ORFs derived from non-coding transcripts produce (micro)proteins, while other studies failed to find evidence for such types of non-canonical translation products. Here, we attempted to discover translation products from non-coding regions by strongly reducing the complexity of the sample prior to mass spectrometric analysis. We used an extended database as the search space and applied stringent filtering of the identified peptides to find evidence for novel translation events. Theoretically, we show that our strategy facilitates the detection of translation events of transcripts from non-coding regions, but experimentally only find 19 peptides (less than 1% of all identified peptides) that might originate from such translation events. Virotrap based interactome analysis of two N-terminal proteoforms originating from non-coding regions finally showed the functional potential of these novel proteins.

scholarly journals Selection Pressure in Alternative Reading Frames

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e108768 ◽  
Author(s):  
Katharina Mir ◽  
Steffen Schober
Keyword(s):  
Selection Pressure ◽  
Alternative Reading Frames ◽  
Alternative Reading ◽  
Reading Frames

scholarly journals Influenza A Virus Infection Induces Viral and Cellular Defective Ribosomal Products Encoded by Alternative Reading Frames

2019 ◽  
Vol 202 (12) ◽  
pp. 3370-3380 ◽  
Author(s):  
Damien J. Zanker ◽  
Sara Oveissi ◽  
David C. Tscharke ◽  
Mubing Duan ◽  
Siyuan Wan ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza A Virus Infection ◽  
Alternative Reading Frames ◽  
Alternative Reading ◽  
Reading Frames

scholarly journals Ribosomal scanning past the primary initiation codon as a mechanism for expression of CTL epitopes encoded in alternative reading frames.

1996 ◽  
Vol 184 (4) ◽  
pp. 1319-1329 ◽  
Author(s):  
T N Bullock ◽  
L C Eisenlohr
Keyword(s):  
Mhc Class I ◽  
Mutational Analysis ◽  
Class I ◽  
Initiation Codon ◽  
Initiation Of Translation ◽  
Cryptic Epitope ◽  
Alternative Reading Frames ◽  
Alternative Reading ◽  
Reading Frames ◽  
Mhc Class I Molecules

An increasing amount of evidence has shown that epitopes restricted to MHC class I molecules and recognized by CTL need not be encoded in a primary open reading frame (ORF). Such epitopes have been demonstrated after stop codons, in alternative reading frames (RF) and within introns. We have used a series of frameshifts (FS) introduced into the Influenza A/PR/8 /34 nucleoprotein (NP) gene to confirm the previous in vitro observations of cryptic epitope expression, and show that they are sufficiently expressed to prime immune responses in vivo. This presentation is not due to sub-dominant epitopes, transcription from cryptic promoters beyond the point of the FS, or internal initiation of translation. By introducing additional mutations to the construct exhibiting the most potent presentation, we have identified initiation codon readthrough (termed scanthrough here, where the scanning ribosome bypasses the conventional initiation codon, initiating translation further downstream) as the likely mechanism of epitope production. Further mutational analysis demonstrated that, while it should operate during the expression of wild-type (WT) protein, scanthrough does not provide a major source of processing substrate in our system. These findings suggest (i) that the full array of self- and pathogen-derived epitopes available during thymic selection and infection has not been fully appreciated and (ii) that cryptic epitope expression should be considered when the specificity of a CTL response cannot be identified or in therapeutic situations when conventional CTL targets are limited, as may be the case with latent viral infections and transformed cells. Finally, initiation codon readthrough provides a plausible explanation for the presentation of exocytic proteins by MHC class I molecules.

scholarly journals Initiation Codon Scanthrough versus Termination Codon Readthrough Demonstrates Strong Potential for Major Histocompatibility Complex Class I–restricted Cryptic Epitope Expression

1997 ◽  
Vol 186 (7) ◽  
pp. 1051-1058 ◽  
Author(s):  
Timothy N.J. Bullock ◽  
Anthony E. Patterson ◽  
Laura L. Franlin ◽  
Evangelia Notidis ◽  
Laurence C. Eisenlohr
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Untranslated Regions ◽  
Complex Class ◽  
Reading Frame ◽  
Histocompatibility Complex ◽  
Cryptic Epitope ◽  
Alternative Reading Frames ◽  
Alternative Reading ◽  
Reading Frames

Accumulating evidence shows that the repertoire of major histocompatibility complex class I–restricted epitopes extends beyond conventional translation reading frames. Previously, we reported that scanthrough translation, where the initiating AUG of a primary open reading frame is bypassed, is most likely to account for the presentation of cryptic epitopes from alternative reading frames within the influenza A PR/8/34 nucleoprotein gene. Here, we confirm and extend these findings using an epitope cassette construct that features two well-defined CD8+ T cell (TCD8+) epitopes in alternative reading frames, each preceded by a single start codon. Expression of one epitope depends on scanning of the ribosome over the first AUG with translation initiation occurring at the second AUG. We find that scanthrough translation has great potency in our system, with its impact being modulated, as predicted, by the base composition surrounding the first initiation codon, the number of start codons preceding the point of alternate reading frame initiation, and the efficiency with which the epitope itself is generated. Additionally, we investigated the efficiency of eukaryotic translation termination codons, to assess codon readthrough as a mechanism for cryptic epitope expression from 3′ untranslated regions. In contrast with initiation codons, eukaryotic stop codons appear to be highly efficient at preventing expression of epitopes encoded in 3′ untranslated regions, suggesting that 3′ untranslated regions are not a common source of cryptic epitope substrate. We conclude that scanthrough is a powerful mechanism for the expression of epitopes encoded in upstream alternative open reading frames that may contribute significantly to TCD8+ responses and to tolerance induction.

scholarly journals Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans

2008 ◽  
Vol 40 (11) ◽  
pp. 1335-1340 ◽  
Author(s):  
Zubair M Ahmed ◽  
Saber Masmoudi ◽  
Ersan Kalay ◽  
Inna A Belyantseva ◽  
Mohamed Ali Mosrati ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Nonsyndromic Deafness ◽  
Alternative Reading Frames ◽  
Alternative Reading ◽  
Reading Frames

scholarly journals Identification of Cryptic MHC I–restricted Epitopes Encoded by HIV-1 Alternative Reading Frames

2004 ◽  
Vol 199 (8) ◽  
pp. 1053-1063 ◽  
Author(s):  
Sylvain Cardinaud ◽  
Arnaud Moris ◽  
Michèle Février ◽  
Pierre-Simon Rohrlich ◽  
Laurence Weiss ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Open Reading Frames ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Alternative Reading Frames ◽  
Anti Hiv ◽  
Alternative Reading ◽  
Reading Frames ◽  
Hiv 1

Human immunodeficiency virus (HIV) 1 major histocompatibility complex (MHC) I–restricted epitopes are widely believed to be derived from viral proteins encoded by primary open reading frames. However, the HIV-1 genome contains alternative reading frames (ARFs) potentially encoding small polypeptides. We have identified a panel of epitopes encoded by ARFs within the gag, pol, and env genes. The corresponding epitopic peptides were immunogenic in mice humanized for MHC-I molecules. In addition, cytotoxic T lymphocytes recognizing these epitopes were found in HIV-infected patients. These results reveal the existence of atypical mechanisms of HIV-1 epitope generation. They indicate that the repertoire of epitopes recognized by the cellular anti–HIV-1 immune response is broader than initially thought. This should be taken into account when designing vaccine strategies aimed at activating these responses.

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